French Academic Strengths in Epigenetics and Cancer

Innovative Projects for International Business Opportunities
and R&D Collaborations
Projects Book 2nd Edition
February 2016
Strategic Tech Transfer Field:
Therapeutic Innovation in Oncology
Yoann Schumacher, Ph.D., Project Manager
yoann.schumac[email protected]
Melina Gaffré, Ph.D., Coordinator, Inserm Transfert
[email protected]
FRENCH ACADEMIC
STRENGTHS IN
EPIGENETICS AND CANCER

2
INTRODUCTION
The Thematic Tech Transfer Consortium (aka Consortium de Valorisation Thématique or
CVT in French) from the national alliance in life sciences, Aviesan, aims to coordinate
the policies, strengths and expertises of its stakeholders* in the fields of life science
and health. This is developed through several Strategic Tech Transfer Fields (aka Domaine
de Valorisation Stratégique or DVS in French) whose goal is to provide national analyses and
actions for their scientific and industrial communities, and to promote partnering opportunities.
The DVS “Therapeutic Innovation in Oncology”, in particular, is supported by Inserm Transfert
and Institut Curie and is dedicated to facilitate the transfer of academic innovations in onco-
logy to the Industry. For this purpose, the DVS has focused its actions on two axis: the identi-
fication of novel and innovative epigenetic targets and the development of focalized therapies
for treating cancer.
Concerning the epigenetic targets, the mains objectives of the DVS are:
1. Stimulate and facilitate the setting up of partnerships between industrials and academics by:
> Mapping and gathering the French academic expertises in epigenetics
> Mapping both academic and industrial French Intellectual Property in epigenetic target
validation
> Analyzing industrial needs
> Identifying potential collaborative R&D projects
> Contributing to build, develop and maintain a trusted relation between academics and
industry
> Boosting the development of novel therapeutic approaches
2. Identify main technology transfer hurdles in this axis
3. Contribute to maintain the visibility of France in this innovative theme.
Directly in line with these objectives, the DVS “Therapeutic Innovation in Oncology” has gathered
in this book innovative projects to highlight French academic strengths in epigenetics and to:
> Enhance the visibility of French research in epigenetics
> Trigger collaborations between researchers
> Facilitate Industry-Academia Partnerships

3
SOMMAIRE
•> 4 Geneviève ALMOUZNI & Zachary GURARD-
LEVIN
Chromatin Dynamics
•> 7 Paola B. ARIMONDO
Epigenetic Targeting of Cancer
•> 10 Catherine BAUGÉ
Chondrosarcomas: Physiopathology and Innovative
Therapies
•> 13 Olivier BERNARD
Normal and malignant hematopoises
•> 15 Philippe BERTRAND
HDAC inhibitors and their delivery
•> 17 Pierre-François CARTRON
Design of a new generation of epidrugs targeting
certains selective interactions between an
epigenetic protein and one of its partner
•> 20 Jean CAVARELLI
Structural Biology of Epigenetic Targets
•> 21 Hervé CHNEIWEISS
Plasticity and Development of Human Brain Tumor
•> 24 Françoise DANTZER & Valérie SCHREIBER
Poly(ADP-ribosyl)ation and genome integrity
•> 27 Estelle DUPREZ
Epigenetic control of normal and pathological
hematopoiesis
•> 30 Reini FERNANDEZ DE LUCO
Epigenetic and Alternative Splicing
•> 33 Pierre FERRIER
Deciphering functional activity of TLX homeodomain
oncogenes in T-cell Acute Leukemia (T-ALL):
Epigenetic analysis
•> 34 Hinrich GRONEMEYER
Systems biology of cell fate decisions in normal and
tumor cells
•> 39 Christophe François GROSSET
Regulation of Genes by microRNAs in Cancer and
Development
•> 42 Dominique GUENOT
Impact of hypoxia and microenvironment in tumor
progression and response to treatment. Translational
approaches and epidemiology
•> 45 Christel GUILLOUF
PU.1 transcription factor in epigenetic and splicing
regulation
•> 48 Zdenko HERCEG
Epigenome deregulation and cancer : mechanisms
and biomarkers
•> 51 Eric JULIEN
Functions of lysine methylation pathways
•> 54 Saadi KHOCHBIN
Epigenetic and Cell Signaling
•> 57 José Arturo LONDO ñO-VALLEJO
Chromosome instability, epigenetics and microRNAs
•> 60 Jérôme MOREAUX
Epigenetic and genomic instability mining in Multiple
Myeloma to define precision medicine
•> 63 Antonin MORILLON
lncRNA and cancer
•> 66 Jean MOSSER
Integrated Functional Genomic and Biomarkers
•> 69 Christian MUCHARDT
Transcription and Splicing in the Context of
Chromatin
•> 72 Peter MULLIGAN
Epigenetics and Cancer
•> 75 Françoise OCHSENBEIN
Molecular assemblies and genome integrity
•> 78 Benjamin ORY
Genetic and Epigenetic aspects of primary bone
tumors development and bone mineralization
•>82 Yves RENAUDINEAU
B cell diseases and epigenetics
•>85 Claire ROUGEULLE
Non-coding RNAs in development and disease
•>88 Jörg TOST
Laboratory for Epigenetics & Environment
•> 91 Michèle TRABUCCHI
Control of Gene Expression
•> 94 Isabelle VAN SEUNINGEN
Epigenetics and epithelial stemness, differentiation
and carcinogenesis
•> 97 André VERDEL
RNA and Epigenetics
•> 99 Thierry VIROLLE
Molecular basis of glioma cancer stem cells
properties and functional intra tumor heterogeneity
•> 102 Bohdan WASYLYK
Molecular and Cellular Biology of HNSCC and
Prostate Cancer
•> 105 Michael WEBER
Laboratory « Epigenetic Regulation of Cell Identity »
headed by Michael Weber
•> 108 Jonathan WEITZMAN
Epigenetics and Cell Fate

4
Chromatin Dynamics
Grants
• Various research / clinical grants, including 2 european research grants,
• Industrial collaboration,
• ERC grant.
Major publications over the past four years
• Montes de Oca R. et al. (2014) HJURP, a CENP-A chaperone as a new
prognostic factor in luminal A breast carcinoma. Mol. Oncol., in press.
Müller S. et al. (2014). Phosphorylation and DNA-binding of HJURP deter-
mine its centromeric recruitment and function in CenH3CENP-A loading.
Cell Rep., 8, 190-203.
Lacoste N. et al. (2014). Mislocalization of the centromeric histone variant
CenH3/CENP-A in human cells depends on the chaperone DAXX. Mol.
Cell, 53, 631-644.
Adam S. et al. (2013). Transcription recovery after DNA damage requires
chromatin priming by the H3.3 histone chaperone HIRA. Cell, 155, 94-106.
Casanova M. et al. (2013). Heterochromatin reorganization during early
mouse development requires a single-strand non-coding transcript. Cell
Rep., 4, 1156-1167.
Patents
• 4 patients available for licencing.
Geneviève ALMOUZNI
& Zachary GURARD-LEVIN
> Research Center; Town: Institut Curie, Paris
> Administrative affiliations: Institut Curie - CNRS UMR 3664
> Tech Transfer Office: Institut Curie
www.curie.fr Keywords:
• Chromatin dynamics
• Chaperones
• Genome stability
• Centromeres
• Epigenetics
Ph.D.
Contact: [email protected]
Synopsis:
Our team is interested in understanding how chromatin organization is established, propagated, maintained,
and changed during development and in response to environmental cues. Errors in these processes can lead
to mis-regulation of genome functions and pathological outcomes, such as cancer.
Abstract:
We study how chromatin organization is established, propagated, maintained, and changed during development
and in response to environmental cues. Errors in these processes can lead to mis-regulation of genome
function and pathological outcomes, such as cancer. We have dissected the mechanisms of chromatin
assembly, from the basic structural unit, the nucleosome, to higher-order nuclear structures. We revealed the
importance of key chaperones involved in nucleosome assembly including histone management and their
specific marks typical of particular chromatin domains. We integrate these findings with dynamic changes
during cell cycle/repair and differentiation and their consequences for nuclear organization and pathologies.
SELECTED REFERENCES

5
Geneviève ALMOUZNI
& Zachary GURARD-LEVIN
Business Development opportunities
Objectives:
• We study how chromatin organization is established, propagated, maintained, and
changed during development and in response to environmental cues. Errors in these
processes can lead to mis-regulation of genome function and pathological outcomes,
such as cancer.
Tools:
• SNAP-tagging and imaging
• ChIP and ChIP-seq
• RNA interference in cultured cells
• Protein complexes purification from cells stably expressing tagged-factors
• Micro-injection / manipulation of Xenopus and mouse early embryos (2 cell stage) and
follow-up of development
• Advance 3D and time-lapse fluorescence microscopy
• Transgenic / KO mouse models
• Bio-computing analysis of high-throuput sequencing / expression data
• Analysis of the dynamics of factors in
vivo by SNAP-Tag and imaging including FRAP,
local damage
• Annotated samples, tumor library
• Cohort of patients with their follow-up
Unique selling points:
• Our team has over 20 years of expertise in chromatin, nuclear organization, replication
repair and development.
• We have dissected the mechanisms of chromatin assembly, from the basic structural
unit, the nucleosome, to higher-order nuclear structures. We revealed the importance
of key chaperones involved in nucleosome assembly including histone management
and their specific marks typical of particular chromatin domains. We integrate these
findings with dynamic changes during cell cycle/repair and differentiation and their
consequences for nuclear organization and pathologies.
Chromatin Dynamics